Intracellular accumulations of lipofuscin (aging pigment) occur gradually with age and can be accelerated by vitamin E deficiency as a model for this aspect of aging. Supposedly, lipofuscin originates from highly oxidized cell products which polymerize and form insoluble, autofluorescent granules within the cytoplasm. Our studies confirm the classical concept that membrane lipids containing polyunsaturated fatty acids (PUFA) contribute significantly to liopofuscin formation in the retinal pigment epithelium (RPE). However, dietary levels of vitamin A appear to be even more important in determining the rate of lipofuscin accumulation. Even a RPE with no source of ingestable rod outer segment membranes which contain PUFA will accumulate large amounts of lipofiscin in a relatively short time if the level of vitamin A is high, but will accumulate almost none if vitamin A is absent. In fact, the RPE of rats fed different amounts of vitamin A (23, 2.3, .23, .058 and 0.0 mg retinol/kg diet) showed a dose-related response with respect to the amount of lipofuscin accumulate. Thus, for the first time, it appears that vitamin A has a direct involvement in lipofuscin formation, and even may become included in lipofuscin granules as one of the oxidized byproducts of cell metabolism.